Quantification of Cell Movement Reveals Distinct Edge Motility Types During Cell Spreading

Actin-based motility is central to cellular processes such as migration, bacterial engulfment, and cancer metastasis, and requires precise spatial and temporal regulation of the cytoskeleton. We studied one such process, fibroblast spreading, which involves three temporal phases: early, middle, and late spreading, distinguished by differences in cell area growth. In these studies, aided by improved algorithms for analyzing edge movement, we observed that each phase was dominated by a single, kinematically and biochemically distinct cytoskeletal organization, or motility type. Specifically, early spreading was dominated by periodic blebbing; continuous protrusion occurred predominantly during middle spreading; and periodic contractions were prevalent in late spreading. Further characterization revealed that each motility type exhibited a distinct distribution of the actin-related protein VASP, while inhibition of actin polymerization by cytochalasin D treatment revealed different dependences on barbed-end polymerization. Through this detailed characterization and graded perturbation of the system, we observed that although each temporal phase of spreading was dominated by a single motility type, in general cells exhibited a variety of motility types in neighboring spatial domains of the plasma membrane edge. These observations support a model in which global signals bias local cytoskeletal biochemistry in favor of a particular motility type

Angular magnetoresistance oscillations in bilayers in tilted magnetic fields

Angular magnetoresistance oscillations (AMRO) were originally discovered in organic conductors and then found in many other layered metals. It should be possible to observe AMRO to semiconducting bilayers as well. Here we present an intuitive geometrical interpretation of AMRO as the Aharonov-Bohm interference effect, both in real and momentum spaces, for balanced and imbalanced bilayers. Applications to the experiments with bilayers in tilted magnetic fields in the metallic state are discussed. We speculate that AMRO may be also observed when each layer of the bilayer is in the composite-fermion state.Comment: 4 pages, 5 figures, Proceedings of EP2DS-16. V.2: figures corrected, one reference added. V3: one reference adde

Climate, Deer, Rodents, and Acorns as Determinants of Variation in Lyme-Disease Risk

Risk of human exposure to vector-borne zoonotic pathogens is a function of the abundance and infection prevalence of vectors. We assessed the determinants of Lyme-disease risk (density and Borrelia burgdorferi-infection prevalence of nymphal Ixodes scapularis ticks) over 13 y on several field plots within eastern deciduous forests in the epicenter of US Lyme disease (Dutchess County, New York). We used a model comparison approach to simultaneously test the importance of ambient growing-season temperature, precipitation, two indices of deer (Odocoileus virginianus) abundance, and densities of white-footed mice (Peromyscus leucopus), eastern chipmunks (Tamias striatus), and acorns ( Quercus spp.), in both simple and multiple regression models, in predicting entomological risk. Indices of deer abundance had no predictive power, and precipitation in the current year and temperature in the prior year had only weak effects on entomological risk. The strongest predictors of a current year's risk were the prior year's abundance of mice and chipmunks and abundance of acorns 2 y previously. In no case did inclusion of deer or climate variables improve the predictive power of models based on rodents, acorns, or both. We conclude that interannual variation in entomological risk of exposure to Lyme disease is correlated positively with prior abundance of key hosts for the immature stages of the tick vector and with critical food resources for those hosts

Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case–parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10×10−6 in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79×10−7). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma

Law of Spirit and Flesh: The Law of Kings and Legal Development in Early-Modern, Christian Ethiopia

This dissertation examines the history of the Ethiopian Orthodox legal text known as theFətḥa N�g�śt (Law of Kings) and its practical application in early-modern Ethiopia. The Fətḥa N�g�śt is considered by many to be the principle legal text in the organization of Ethiopian Christian society. Yet scholarship on the Fətḥa N�g�śt’s role in Ethiopia is quite divided with many downplaying its importance. I argue that the Fətḥa N�g�śt is the foundational legal text in a complex legal system that developed over centuries in Christian Ethiopia. First, I focus on the origins of the legal text, from its composition in the thirteenth century in Coptic Egypt, to the translation and adoption of the text in Ethiopia. Local stories of the origin of the code in Ethiopia, place its promulgation in the mid to late-fifteenth century. I consider an earlier date for the promulgation, in the early-fourteenth to early-fifteenth century. This is based on evidence drawn from a variety of sources, including Ethiopian Orthodox hagiographies and European travel narratives. Second, I explore the institutions that facilitated the adoption and integration of this text into the legal landscape of Ethiopia. The Ethiopian Orthodox Church developed centers of legal education where scholars were trained to deliver justice based on the provisions in the Fətḥa N�g�śt. Throughout the fifteenth and sixteenth centuries, complex interpretation systems developed out of the commentary traditions taught in the schools of the Ethiopian Orthodox Church. The scholars who were trained in the interpretation of the Fətḥa N�g�śt in the law school of the Church went on to fill the most important administrative positions in the kingdom. Finally, I look at case studies from the eighteenth to twentieth centuries. The case studies involve slavery, manumission, usury and property. These cases reveal a well-developed legal system heavily influenced by the Fətḥa N�g�śt. The system is blended and contains fluid boundaries between the ‘secular’ and ‘religious,’ and accordingly aligns with the Ethiopian Christian concept of law as intrinsically sacred in character

One Law for Us All: A History of Social Cohesion through Shared Legal Tradition Among the Abrahamic Faiths in Ethiopia

This thesis historically traces the development and interactions of Christianity, Judaism, and Islam in Ethiopia. This analysis of the interactions between the Abrahamic faiths is primarily concerned with identifying notable periods of social cohesion in an effort to contest mainstream narratives that often pit the three against each other. This task is undertaken by incorporating a comparative analysis of the Ethiopian Christian code, the Fetha Nagast (Law of Kings), with Islamic and Judaic legal traditions. Identifying the common threads weaved throughout the Abrahamic legal traditions demonstrates how the historical development and periods of social cohesion in Ethiopia were facilitated

Measuring evolutionary rates of proteins in a structural context [version 1; referees: 3 approved]

We describe how to measure site-specific rates of evolution in protein-coding genes and how to correlate these rates with structural features of the expressed protein, such as relative solvent accessibility, secondary structure, or weighted contact number. We present two alternative approaches to rate calculations, one based on relative amino-acid rates and the other based on site-specific codon rates measured as dN/dS. In addition to describing the specific analysis protocols we recommend, we also provide a code repository containing scripts to facilitate these kinds of analyses

Measuring evolutionary rates of proteins in a structural context [version 2; referees: 4 approved]

We describe how to measure site-specific rates of evolution in protein-coding genes and how to correlate these rates with structural features of the expressed protein, such as relative solvent accessibility, secondary structure, or weighted contact number. We present two alternative approaches to rate calculations: One based on relative amino-acid rates, and the other based on site-specific codon rates measured as dN/dS. We additionally provide a code repository containing scripts to facilitate the specific analysis protocols we recommend